Thermoresponsive Hydrogel Research Articles

Hydrogel Rivet with Unidirectional Shape Morphing for Flexible Mechanical Assembly.

Integrating diverse materials and functions into highly additive produce has piqued global interest due to the increasing demands of intelligent soft robotics. Nevertheless, existing assembly techniques, especially supramolecular assembly which heavily rely on precise chemical design and specific recognition, may prove inadequate when confronted with diverse external demands. Inspired by the traditional mechanical assembly, rivet connection, herein, a thermo-responsive hydrogel with unidirectional shape-morphing is fabricated and a stable mechanical assembly is constructed by emulating the rivet connection mechanism. This system employed poly(acrylamide-co-acrylic acid) [P(AAm-co-AAc)] to induce continuous swelling and hexylamine-modified polyvinyl alcohol (PVA-C6) as a molecular switch to control the swelling process. The hydrogel rivet, initially threaded through pre-fabricated hollows in two components. Subsequently, upon the disassociation of alkane chainsthe molecular switch would activate, inducing swelling and stable mechanical assembly via anchor structures. Moreover, to enhance the assembly strength, knots are introduced to enhance assembly strength, guiding localized stress release for programmed deformations. Additionally, the system can be remotely controlled using near-infrared light (NIR) by incorporating photo-thermal nanoparticles. This work presents a universal and efficient strategy for constructing stable mechanical assemblies without compromising overall softness, offering significant potential for the fabrication of integrated soft robots.

Abstract 16714: An Injectable Thermo-Responsive Hydrogel as a Tool for Cardiac Tissue Engineering Efforts: In vitro and in vivo Biocompatibility Assessment

Background: Heart failure (HF) is a major contributor to the global burden of cardiovascular disease. Current treatments for HF do not regenerate muscle nor function and so cardiac transplantation remains the only definitive treatment for HF. Thus, novel therapies for HF are still needed. To overcome this limitation, we engineered an injectable thermo-responsive hydrogel that transitions from a liquid-solution to a gel-based matrix upon reaching body temperature allowing for a liquid injection rapidly followed by gel localization. Previously, we demonstrated the potential of our hydrogel for cardiac tissue applications using primary cardiomyocytes. Goal: The goal of this project is to assess the biocompatibility of the thermo-responsive hydrogel with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and its effect on mice heart tissue. Methods: 3D cell culture: 9x104 hiPSC-CM were encapsulated for 21 days using 150μl of hydrogel solution (1.5% w/w) and cell function was assessed afterwards. Mouse intracardial injection: a left thoracotomy was performed via the fourth intercostal space in an adult C57BL/6 mouse model. Then, three injections of 10 μl of either (i) lipofectamine, (ii) hydrogel (1% w/w) or (ii) saline were injected into the left ventricle anterior wall. After injections, the thoracotomy site was closed, and the animals recovered. Four weeks post inject the tissues were harvested and prepared for studies. Results: We found that our hydrogel promotes hiPSC-CMs alignment, elongation with increased Cx43 localization and improved contraction function when compared with traditional 2D fibronectin controls. Furthermore, the in-vivo biocompatibility in mice (intracardial injection) proved that our hydrogel is well tolerated by cardiac tissue. Conclusion: Our results indicated that the injectable thermos-responsive hydrogel is a biocompatible material with potential to be used in cardiac tissue engineering efforts.

Stimuli-responsive nanoparticles delivered by a nasal-brain pathway alleviate depression-like behavior through extensively scavenging ROS.

Depression is one of the most common mental diseases, which seriously affects patients' physical and mental health. Emerging evidence has indicated that oxidative stress (OS) is a major cause of neurodegeneration involved in the pathogenesis of depression. Consequently, targeted reactive oxygen species (ROS) elimination is regarded as a promising strategy for efficient depression therapy. In addition, insufficient brain drug delivery is the main obstacle to depression therapy owing to the presence of the blood-brain barrier (BBB). To achieve the goals of bypassing the BBB and promoting antioxidant therapy for depression, a broad-spectrum ROS scavenging NPs was rationally designed through a nasal-brain pathway developed for combined ROS scavenging and brain drug delivery. A hexa-arginine (R6) modified ROS-responsive dextran (DEX) derivate was synthesized for antidepressant olanzapine (Olz) and H2 donor amino borane (AB) loading to prepare Olz/RDPA nanoparticles (NPs). Subsequently, the NPs were dispersed into a thermoresponsive hydrogel system based on poloxamer. In vitro and in vivo results demonstrated that Olz/RDPA in situ thermoresponsive hydrogel system could effectively deliver NPs to the brain via the nasal-brain pathway and alleviate depression-like behaviors through combined ROS depletion and inhibition of 5-HT dysfunction of the oxidative stress-induced. The proposed ROS-scavenging nanotherapeutic would open a new window for depression treatment. STATEMENT OF SIGNIFICANCE: ROS is an innovative therapeutic target involving the pathology of depression whereas targeted delivery of ROS scavenging has not been achieved yet. In the current study, ROS-responsive nanoparticles (Olz/RDPA NPs) were prepared and dispersed in a thermosensitive hydrogel for delivery through the nasal-brain pathway for the treatment of depression. Sufficient ROS depletion and improvement of delivery capacity by the nasal-brain pathway effectively could reverse oxidative stress and alleviate depressive-like behavior. Collectively, these nanoparticles may represent a promising strategy for the treatment of depression.

Bone-Adhesive Hydrogel for Effective Inhibition of M. tuberculosis and Osteoblast Regeneration.

Currently, bone tuberculosis (TB) treatment largely involves lifelong drug prescriptions and surgical intervention, resulting in poor quality of life for patients. Therefore, the fabrication of injectable scaffolds to form a solid framework around the defective bone region is gaining importance over the extensive use of antimicrobial inhibitors. Herein, we synthesized a novel bone-adhesive and thermoresponsive hydrogel via conjugation of poly(N-isopropylacrylamide-co-glycidyl methacrylate) (PNIPAM-co-GMA) and cysteine (CYS). Thiolation of the polymer enables chemical cross-linking with the bone glycoprotein, enhancing bone adhesion and permitting control of scaffold retention time. The PNIPAM-co-GMA-CYS hydrogel shows higher cross-linking behavior at 37 °C, forms a strong gel in 260 s, and has 151 kPa adhesion strength on cortical bone. The lead compounds 5-methyl-5H-[1,2,4]triazino[5,6-b]indole-3-thiol (MTIT) and N-tert-butyl-4-methyl-6-(5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-ylthio)pyrimidin-2-amine (TMTIPA) were identified by a high-throughput screening method. Effective MTIT and TMTIPA are encapsulated in bone-adhesive hydrogel separately, and both have a high release rate above >70% in 180 h. The MTIT- and TMTIPA-loaded PNIPAM-co-GMA-CYS showed an excellent bactericidal effect, reducing the relative intracellular bacterial survival in macrophages. Furthermore, the as-synthesized hydrogel has outstanding mechanical and biocompatibility properties to become a bone-replacing material and provide support to promote bone repair. This work presents a novel bone-adhesive PNIPAM-co-GMA-CYS for the sustained release of lead compounds toward promising alternative bone TB treatment.

Thermoresponsive injectable self-healing hydrogel containing polydopamine-coated Fe/Mo-doped TiO2 nanoparticles for efficient synergistic sonodynamic-chemodynamic-photothermal-chemo therapy

A smart hydrogel loading multifunctional nanoparticles and anticancer drugs was designed to achieve synergistic therapy against tumors with high efficiency and specificity. The thermoresponsive injectable self-healing hydrogel was prepared through the Schiff base between aldehyde-functionalized poly(2-(2-methoxyethoxy) ethyl methacrylate)–co-oligo(ethylene glycol) methacrylate-co-2-hydroxyethyl methacrylate) (P(MEO2MA-co-OEGMA-co-HEMA), APMOH) and hydroxypropyl chitosan (HPCS). The polydopamine-coated Fe/Mo-doped titanium dioxide nanoparticles (PDA@dTiO2 NPs) were prepared and dispersed into the hydrogel with anticancer drug doxorubicin (DOX). PDA@dTiO2 NPs as sonosensitizers can convert oxygen into singlet oxygen (1O2) under ultrasound (US) irradiation, achieving sonodynamic therapy (SDT). They were also considered nanoenzymes, generating oxygen to supply an oxygen source for SDT, producing hydroxyl radical (·OH) to achieve chemodynamic therapy (CDT), and eliminating glutathione (GSH) to enhance the level of oxidative stress. After near-infrared (NIR) irradiation, the temperature of the hydrogel increased due to the photothermal ability of the polydopamine (PDA) layer. When the temperature reached the hydrogel's lower critical solution temperature (LCST), the hydrophilic-hydrophobic transformation occurred, and the hydrogel volume contracted. Consequently, the release rate of PDA@dTiO2 NPs and DOX increased, improving the therapeutic effects. The nanocomposite hydrogel system can achieve synergistic sonodynamic-chemodynamic-photothermal-chemo therapy (SDT-CDT-PTT-CT) for tumors, providing a novel platform for synergistic tumor treatment.

Potential of thermoresponsive hydrogel as an alternative therapy for rat knee osteoarthritis.

Osteoarthritis is a degenerative condition that is highly prevalent and primarily affects the joints. The knee is the most commonly affected site, impacting the lives of over 300 million individuals worldwide. This study presents a potential solution to address the unmet need for a minimally invasive technique in the treatment of osteoarthritis: a biocompatible, injectable, and thermoresponsive hydrogel. In comparison to commercially available products such as lyophilized platelets, dextrose, and triamcinolone, the thermoresponsive hydrogel exhibits significantly superior performance in dynamic behaviors, including print area, stability, and step cycle, when tested on rats with knee osteoarthritis. However, it demonstrates similar treatment efficacy to these products in static behaviors, as observed through histopathological and immunohistochemical analysis. Therefore, the thermoresponsive hydrogel holds promise as an effective alternative therapy for osteoarthritis. Moreover, by blending the hydrogel with drugs, controlled and sustained release can be achieved, thereby facilitating the long-term management of osteoarthritis symptoms.

Electrochemically Controlled Release from a Thin Hydrogel Layer.

In this study, we present a thermoresponsive thin hydrogel layer based on poly(N-isopropylacrylamide), functionalized with β-cyclodextrin groups (p(NIPA-βCD)), as a novel electrochemically controlled release system. This thin hydrogel layer was synthesized and simultaneously attached to the surface of a Au quartz crystal microbalance (QCM) electrode using electrochemically induced free radical polymerization. The process was induced and monitored using cyclic voltammetry and a quartz crystal microbalance with dissipation monitoring (QCM-D), respectively. The properties of the thin layer were investigated by using QCM-D and scanning electron microscopy (SEM). The incorporation of β-cyclodextrin moieties within the polymer network allowed rhodamine B dye modified with ferrocene (RdFc), serving as a model metallodrug, to accumulate in the p(NIPA-βCD) layer through host-guest inclusion complex formation. The redox properties of the electroactive p(NIPA-βCD/RdFc) layer and the dissociation of the host-guest complex triggered by changes in the oxidation state of the ferrocene groups were investigated. It was found that oxidation of the ferrocene moieties led to the release of RdFc. It was crucial to achieve precise control over the release of RdFc by applying the appropriate electrochemical signal, specifically, by applying the appropriate potential to the electrode. Importantly, the electrochemically controlled RdFc release process was performed at a temperature similar to that of the human body and monitored using a spectrofluorimetric technique. The presented system appears to be particularly suitable for transdermal delivery and delivery from intrabody implants.

Regulating Electrostatic Interactions toward Thermoresponsive Hydrogels with Low Critical Solution Temperature.

Low critical solution temperature (LCST) of commonly used thermoresponsive polymers in water is basically dominated by hydrophobic interactions. Herein, a novel thermoresponsive system based on electrostatic interactions is reported. By simply loading aluminum chloride (AlCl3 ) into non-responsive poly(2-hydroxyethyl acrylate) (PHEA) hydrogels, PHEA-Al gels turn to have reversible thermoresponsive behavior between transparent and opaque without any volume change. Further investigations by changing metal ion-polymer compositions unravel the necessity of specific electrostatic interactions, namely, cation-dipole bonding interactions between hydroxy groups and trivalent metal ions. The thermoresponsive hydrogel demonstrates high transparency (≈95%), excellent luminous modulation capability (>98%), and cyclic reliability, suggesting great potential as an energy-saving material. Although LCST control by salt addition is widely known, salt-induced expression of thermoresponsiveness has barely been discussed before. This design provides a new approach of easy fabrication, low cost, and scalability to develop stimuli-responsive materials.

In situ injectable thermoresponsive nanocomposite hydrogel based on hydroxypropyl chitosan for precise synergistic calcium-overload, photodynamic and photothermal tumor therapy

Traditional therapies have poor accuracy and significant toxic side effects in the process of tumor treatment. The non-traditional treatment methods with high accuracy and efficacy are worth exploring and investigating. Herein, a strategy that enables precise and synergistic therapies of calcium-overload, photodynamic, and photothermal through facile near infrared (NIR) irradiation was carried out base on the injectable and self-healable hydrogel encapsulating indocyanine green (ICG)-loaded and bovine serum albumin (BSA)-modified calcium peroxide (CaO2) nanoparticles (ICG@CaO2-BSA NPs) and bismuth sulfide (Bi2S3) nanorods. The hydrogel fabricated through the dynamic Schiff-base bonds between hydroxypropyl chitosan (HPCS) and aldehyde-modified Pluronic F127 (F127-CHO) as the delivery substrate for functional substances could adhere and grip tumor tissues due to the adhesion of hydroxyl groups in HPCS and the hydrophobic aggregation caused by thermoresponsiveness of F127-CHO. CaO2 in ICG@CaO2-BSA NPs decomposed in the tumor micro-acidic environment to produce calcium ions (Ca2+) and hydrogen peroxide (H2O2), while ICG generated reactive oxygen species (ROS) under NIR irradiation, the photothermal effect of Bi2S3 nanorods and ICG under NIR irradiation could increase the temperature of tumor tissues and ultimately achieve precise tumor cell destruction. Therefore, this strategy will provide promising prospects for precise and efficient treatment of tumors.

Porous silicon embedded in a thermoresponsive hydrogel for intranasal delivery of lipophilic drugs to treat rhinosinusitis

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively).

Thermoresponsive DNA hydrogels through hydrophilic pre-polymer cross-linker and self-assembly

Denatured DNA molecules were used as building blocks to fabricate thermoresponsive hydrogels by cross-linking DNA strands with an isocyanate (NCO) end-capped star-shaped poly(EO-stat-PO) cross-linker. The NCO groups reacted with the amine groups of DNA’s bases through urea links while base pairing between the matching strands of DNA led to the self-assembly of DNA into a three-dimensional hydrogel network. Analysis of the ultrastructure by scanning force microscopy (SFM) revealed the temperature-mediated transition from the rod-to-coil structure as a result of the destabilization of double-stranded DNA (dsDNA) to form a single-stranded DNA (ssDNA), which eventually resulted in a DNA network due to base pairing, along with hairpin loops due to mismatches between nucleotides. Dynamic oscillatory and large deformation creep tests, as well as stress relaxation tests, revealed the formation of robust cross-linked gels: A ten-fold rise in the elastic modulus was observed for the covalent DNA gel compared to the physical gel at the identical DNA concentration. The thermoresponsiveness of the hydrogels was confirmed by a heating–cooling cycle while the non-porous internal morphology of the hydrogel was demonstrated through scanning electron microscopic analysis. Overall, this is the first study showing the fabrication of covalent DNA hydrogels using an NCO-end-capped hydrophilic prepolymer. Such gels have a high potential to be exploited in many fields to benefit from the structural properties of DNA molecules.

Fabrication of 3D Printed, Core-and-Shell Implants as Controlled Release Systems for Local siRNA Delivery.

The development and clinical translation of small interfering RNA (siRNA) therapies remains challenging owing to their poor pharmacokinetics. 3D printing technology presents a great opportunity to fabricate personalized implants for local and sustained delivery of siRNA. Hydrogels can mimic the mechanical properties of tissues, avoiding the problems associated with rigid implants. Herein, a thermoresponsive composite hydrogel suitable for extrusion 3D-printing is formulated to fabricate controlled-release implants loaded with siRNA-Lipofectamine RNAiMAX complexes. A hydrogel matrix mainly composed of uncharged agarose to protect siRNA from decomplexation is selected. Additionally, pluronic F127 and gelatin are added to improve the printability, degradation, and cell adhesion to the implants. To avoid exposing siRNA to thermal stress during the printing process, a core-and-shell design is set up for the implants in which a core of siRNA-complexes loaded-pluronic F127 is printed without heat and enclosed with a shell comprising the thermoresponsive composite hydrogel. The release profile of siRNA-complexes is envisioned to be controlled by varying the printing patterns. The results reveal that the implants sustain siRNA release for one month. The intactness of the released siRNA-complexes is proven until the eighth day. Furthermore, by changing the printing patterns, the release profiles can be tailored.

Thermo-Responsive Hydrogels Encapsulating Targeted Core-Shell Nanoparticles as Injectable Drug Delivery Systems.

As therapeutic agents that allow for minimally invasive administration, injectable biomaterials stand out as effective tools with tunable properties. Furthermore, hydrogels with responsive features present potential platforms for delivering therapeutics to desired sites in the body. Herein, temperature-responsive hydrogel scaffolds with embedded targeted nanoparticles were utilized to achieve controlled drug delivery via local drug administration. Poly(N-isopropylacrylamide) (pNIPAM) hydrogels, prepared with an ethylene-glycol-based cross-linker, demonstrated thermo-sensitive gelation ability upon injection into environments at body temperature. This hydrogel network was engineered to provide a slow and controlled drug release profile by being incorporated with curcumin-loaded nanoparticles bearing high encapsulation efficiency. A core (alginate)-shell (chitosan) nanoparticle design was preferred to ensure the stability of the drug molecules encapsulated in the core and to provide slower drug release. Nanoparticle-embedded hydrogels were shown to release curcumin at least four times slower compared to the free nanoparticle itself and to possess high water uptake capacity and more mechanically stable viscoelastic behavior. Moreover, this therapy has the potential to specifically address tumor tissues over-expressing folate receptors like ovaries, as the nanoparticles target the receptors by folic acid conjugation to the periphery. Together with its temperature-driven injectability, it can be concluded that this hydrogel scaffold with drug-loaded and embedded folate-targeting nanoparticles would provide effective therapy for tumor tissues accessible via minimally invasive routes and be beneficial for post-operative drug administration after tumor resection.

Designing dynamic metal-coordinated hydrophobically associated mechanically robust and stretchable hydrogels for versatile, multifunctional applications in strain sensing, actuation and flexible supercapacitors

Combining the synergistic effect of dynamic metal–ligand cross-linking and hydrophobic association along with low density chemical cross-linking, we have developed a mechanically robust and stretchable hydrogel that was synthesized by micellar copolymerization of acrylamide (AM), maleic acid (MA) and butyl acrylate monomer. With optimized composition, this hydrogel showed ∼ 3 MPa tensile strength & ∼ 60 MPa compressive strength. The hydrogel is stretchable ∼ 7 times of its original length. These hydrogel materials are flexible and can be folded, bent, and twisted due to their high toughness (∼10 MJ m−3) and low elastic modulus (0.56 MPa). Because of the dynamic nature of metal–ligand interaction and hydrophobic association, the hydrogel showed high energy dissipation under tensile deformation and quick recovery of the dissipated energy after repeated loading and unloading. This hydrogel showed pH responsive mechanical properties. At lower pH, the mechanical strength and elastic modulus of the hydrogel deteriorated due to the dissociation of metal–ligand interaction. This concept was further used for demonstrating shape memory effect in these materials. Utilizing the colorimetric change in presence of Fe3+ and H+, the hydrogel can be used for data encryption-decryption technology. Combining with a thermoresponsive hydrogel (Poly (N-Isopropyl acrylamide)) layer, our hydrogel showed excellent thermoresponsive reversible actuation effect. Furthermore, because of its high ionic conductivity and strain dependent resistance change, the hydrogel can be used as a flexible strain sensor and as a compressible electrolyte in flexible supercapacitor devices.

Photo and temperature responsive novel surface active ionic liquid-based polymeric hydrogel

Integrating more than two properties into a single polymeric hydrogel to introduce the multi-functionality has been a challenge for the scientific community in recent times. In order to impart photo and temperature responsive characteristics added with adjustable mechanical properties into the polymeric hydrogel, herein we have added newly synthesized photo-responsive ionic liquid (IL) into the polymeric (κ-carrageenan) hydrogel. The IL used is having morpholine-based ester functionalized long chain cation and azobenzene based anion that exhibited trans to cis transformation when irradiated by light of 465 nm for 50 min and show surface-active properties with CMC of 6.83 mM. IL with such photo and temperature responsive properties when mixed with the hydrogel of κ-carrageenan in KCl solution gives the photo and thermo-responsive hybrid hydrogel. The three-dimensional network structure of hydrogel made up of the ellipsoidal aggregates with major and minor axis radius of 9.3 A0 and 1.6 A0, respectively is made up of a fibrous porous structure and gets disrupted through the light irradiation and initiated the gel to sol transition, studied through the SEM images, DLS data and rheological measurements. The (IL) based hydrogel gets disrupted after light irradiation as the anion of the IL starts transforming from trans to cis isomerization. Also, the thermo-reversible transition of hydrogel within room temperature to 54 °C is also shown by rheology. Kinetics of the trans to cis transformation, controlled strain and stress measurement and thermal stability of the hydrogel are assessed here. The studied photo and temperature responsive hydrogel could start a new range of smart materials.

A Closed Loop Stimuli-Responsive Concanavalin A-Loaded Chitosan-Pluronic Hydrogel for Glucose-Responsive Delivery of Short-Acting Insulin Prototyped in RIN-5F Pancreatic Cells.

The optimal treatment of diabetes (in particular, type 1 diabetes-T1D) remains a challenge. Closed-loop systems (implants/inserts) provide significant advantages for glucose responsivity and providing real-time sustained release of rapid-acting insulin. Concanavalin A (ConA), a glucose affinity agent, has been used to design closed-loop insulin delivery systems but not without significant risk of leakage of ConA from the matrices and poor mechanical strength of the hydrogels impacting longevity and control of insulin release. Therefore, this work focused on employing a thermoresponsive co-forming matrix between Pluronic F-127 (PL) and structurally robust chitosan (CHT) via EDC/NHS coupling (i.e., covalent linkage of -NH2 from CHT and ConA to the -COOH of PL). The system was characterized for its chemical structure stability and integrity (FTIR, XRD and TGA), injectability, rheological parameters and hydrogel morphology (Texture Analysis, Elastosens TM Bio2 and SEM). The prepared hydrogels demonstrated shear-thinning for injectability with a maximum force of 4.9 ± 8.3 N in a 26G needle with sol-gel transitioning from 25 to 38 °C. The apparent yield stress value of the hydrogel was determined to be 67.47 Pa. The insulin loading efficiency within the hydrogel matrix was calculated to be 46.8%. Insulin release studies revealed glucose responsiveness in simulated glycemic media (4 and 10 mg/mL) over 7 days (97%) (305 nm via fluorescence spectrophotometry). The MTT studies were performed over 72 h on RIN-5F pancreatic cells with viability results >80%. Results revealed that the thermoresponsive hydrogel is a promising alternative to current closed-loop insulin delivery systems.

Molecularly confined hydration in thermoresponsive hydrogels for efficient atmospheric water harvesting

Water scarcity is a pressing global issue, requiring innovative solutions such as atmospheric water harvesting (AWH), which captures moisture from the air to provide potable water to many water-stressed areas. Thermoresponsive hydrogels, a class of temperature-sensitive polymers, demonstrate potential for AWH as matrices for hygroscopic components like salts predominantly due to their relatively energy-efficient desorption properties compared to other sorbents. However, challenges such as limited swelling capacity due to the salting-out effect and difficulty in more complete water release hinder the effectiveness of conventional hydrogel sorbents. To overcome these limitations, we introduce molecularly confined hydration in thermoresponsive hydrogels by employing a bifunctional polymeric network composed of hygroscopic zwitterionic moieties and thermoresponsive moieties. Here, we show that this approach ensures stable water uptake, enables water release at relatively low temperatures, and exhibits rapid sorption-desorption kinetics. Furthermore, by incorporating photothermal absorbers, the sorbent can achieve solar-driven AWH with comparable water release performance. This work advances the design of AWH sorbents by introducing molecularly confined hydration in thermoresponsive hydrogels, leading to a more efficient and sustainable approach to water harvesting. Our findings offer a potential solution for advanced sorbent design with comprehensive performance to mitigate the freshwater crisis.

Tunable random lasers via phase transition for information encryption

Introducing phase transition materials to random systems provides a promising route to create new optoelectronic functionalities of random lasers. Here, a phase transition random laser with switchable lasing modes is reported, which is designed with a thermoresponsive hydrogel as scattering medium. By manipulating the phase transition in hydrogel, random lasing modes can be switched reversibility between incoherent and coherent random lasing. The phenomenon derives from the changing of light scattering properties in different phase states, thus affecting the optical feedback path of random lasing. Besides, based on its controllable and easily detectable time-domain characteristics, the phase transition random laser is applied in information encoding and transmission. It is the first time that the transition from coherent to incoherent random lasing is observed by varying the sample phase states. This work will inspire the design and application of novel random lasers in photoelectric device.

Injectable pH and Thermo-Responsive Hydrogel Scaffold with Enhanced Osteogenic Differentiation of Preosteoblasts for Bone Regeneration.

Bone fractures are common in the geriatric population and pose a great economic burden worldwide. While traditional methods for repairing bone defects have primarily been autografts, there are several drawbacks limiting its use. Bone graft substitutes have been used as alternative strategies to improve bone healing. However, there remain several impediments to achieving the desired healing outcomes. Injectable hydrogels have become attractive scaffold materials for bone regeneration, given their high performance in filling irregularly sized bone defects and their ability to encapsulate cells and bioactive molecules and mimic the native ECM of bone. We investigated the use of an injectable chitosan-based hydrogel scaffold to promote the differentiation of preosteoblasts in vitro. The hydrogels were characterized by evaluating cell homogeneity, cell viability, rheological and mechanical properties, and differentiation ability of preosteoblasts in hydrogel scaffolds. Cell-laden hydrogel scaffolds exhibited shear thinning behavior and the ability to maintain shape fidelity after injection. The CNC-CS hydrogels exhibited higher mechanical strength and significantly upregulated the osteogenic activity and differentiation of preosteoblasts, as shown by ALP activity assays and histological analysis of hydrogel scaffolds. These results suggest that this injectable hydrogel is suitable for cell survival, can promote osteogenic differentiation of preosteoblasts, and structurally support new bone growth.

Dendronized chitosan hydrogel with GIT1 to accelerate bone defect repair through increasing local neovascular amount

Bone defects have long been a major healthcare issue because of the difficulties in regenerating bone mass volume and the high cost of treatment. G protein-coupled receptor kinase 2 interacting protein 1 (GIT1) has been proven to play an important role both in vascular development and in bone fracture healing. In this study, a type of thermoresponsive injectable hydrogel from oligoethylene glycol-based dendronized chitosan (G1-CS) was loaded with GIT1-plasmids (G1-CS/GIT1), and used to fill unicortical bone defects. RT-PCR analysis confirmed that G1-CS/GIT1 enhanced DNA transfection in MSCs both in vitro and in vivo. From the results of micro-CT, RT-PCR and histological analysis, it can be concluded that G1-CS/GIT1 accelerated the bone healing rate and increased the amount of neovascularization around the bone defects. In addition, an adeno-associated virus (AAV)-GIT1 was constructed to transfect mesenchymal stem cells. The results of capillary tube formation assay, immunofluorescence staining and western blot analysis proved that high expression of GIT1 induces mesenchymal stem cells to differentiate into endothelial cells. RT-PCR analysis and capillary tube formation assay confirmed that the Notch signaling pathway was activated in the differentiation process. Overall, we developed an efficient strategy through combination of injectable hydrogel and G1T1 for bone tissue engineering.